Enlighten
Research publications by members of the University of Glasgow
home > services > Enlighten

The role of interleukin 12 and nitric oxide in the development of spontaneous autoimmune disease in MRL/MP-lpr/lpr mice

Huang, F.P., Feng, G.J., Lindop, G., Stott, D.I., and Liew, F.Y. (1996) The role of interleukin 12 and nitric oxide in the development of spontaneous autoimmune disease in MRL/MP-lpr/lpr mice. Journal of Experimental Medicine, 183 (4). pp. 1447-1459. ISSN 1540-9538

[img]
Preview
Text
stott3634.pdf

4Mb

Publisher's URL: http://www.jem.org/content/vol183/issue4/index.shtml

Abstract

MRL/MP-lpr/lpr (MRL/lpr) mice develop a spontaneous autoimmune disease. Serum from these mice contained significantly higher concentrations of nitrite/nitrate than serum from age-matched control MRL/MP-+/+ (MRL/+), BALB/c or CBA/6J mice. Spleen and peritoneal cells from MRL/lpr mice also produced significantly more nitric oxide (NO) than those from the control mice when cultured with interferon (IFN) gamma and lipopolysaccharide (LPS) in vitro. It is interesting to note that peritoneal cells from MRL/lpr mice also produced markedly higher concentrations of interleukin (IL) 12 than those from MRL/+ or BALB/c mice when cultured with same stimuli. It is striking that cells from MRL/lpr mice produced high concentrations of NO when cultured cells from MRL/+ or BALB/c mice. The enhanced NO synthesis induced by IFN- gamma/LPS was substantially inhibited by anti-IL-12 antibody. In addition, IL-12-induced NO production can also be markedly inhibited by anti-IFN-gamma antibody, but only weakly inhibited by anti-tumor necrosis factor alpha antibody. The effect of IL-12 on NO production was dependent on the presence of natural killer and possibly T cells. Serum from MRL/lpr mice contained significantly higher concentrations of IL-12 compared with those of MRL/+ or BALB/c control mice. Daily injection of recombinant IL-12 led to increased serum levels of IFN- gamma and NO metabolites, and accelerated glomerulonephritis in the young MRL/lpr mice (but not in the MRL/+ mice) compared with controls injected with phosphate-buffered saline alone. These data, together with previous finding that NO synthase inhibitors can ameliorate autoimmune disease in MRL/lpr mice, suggest that high capacity of such mice to produce IL-12 and their greater responsiveness to IL-12, leading to the production of high concentrations of NO, are important factors in this spontaneous model of autoimmune disease.

Item Type:Article
Status:Published
Refereed:Yes
Glasgow Author(s):Liew, Prof Foo and Stott, Prof David
Authors: Huang, F.P., Feng, G.J., Lindop, G., Stott, D.I., and Liew, F.Y.
Subjects:Q Science > QR Microbiology > QR180 Immunology
College/School:College of Medical Veterinary and Life Sciences
College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Journal of Experimental Medicine
Publisher:Rockefeller University Press
ISSN:1540-9538
Copyright Holders:Copyright © 1996 Rockefeller University Press
First Published:First published The Journal of Experimental Medicine 183: 1447-1459
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher.

University Staff: Request a correction | Enlighten Editors: Update this record

Downloads per month over past year

View more statistics